AUTHOR=Oehmcke-Hecht Sonja , Nass Leif E. , Wichura Jan B. , Mikkat Stefan , Kreikemeyer Bernd , Fiedler Tomas 

TITLE=Deletion of the L-Lactate Dehydrogenase Gene ldh in Streptococcus pyogenes Leads to a Loss of SpeB Activity and a Hypovirulent Phenotype

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01841

DOI=10.3389/fmicb.2017.01841

ISSN=1664-302X

ABSTRACT=<p><italic>Streptococcus pyogenes</italic> uses lactic acid fermentation for the generation of ATP. Here, we analyzed the impact of a deletion of the <sc>L</sc>-lactate dehydrogenase gene <italic>ldh</italic> on the virulence of <italic>S. pyogenes</italic> M49. While the <italic>ldh</italic> deletion does not cause a general growth deficiency in laboratory media, the growth in human blood and plasma is significantly hampered. The <italic>ldh</italic> deletion strain is furthermore less virulent in a <italic>Galleria mellonella</italic> infection model. We show that the <italic>ldh</italic> deletion leads to a decrease in the activity of the cysteine protease SpeB, an important secreted virulence factor of <italic>S. pyogenes</italic>. The reduced SpeB activity is caused by a hampered autocatalytic activation of the SpeB zymogen into the mature SpeB. The missing SpeB activity furthermore leads to increased plasmin activation and a reduced activation of the contact system on the surface of <italic>S. pyogenes</italic>. All these effects can be reversed when <italic>ldh</italic> is reintroduced into the mutant via a plasmid. The results demonstrate a previously unappreciated role for LDH in modulation of SpeB maturation.</p>